Clinical and prognostic significance of circulating levels of angiopoietin-1 and angiopoietin-2 in hepatocellular carcinoma

// Roberto Carmagnani Pestana 1 , Manal M. Hassan 2 , Reham Abdel-Wahab 3, 7 , Yehia I. Abugabal 3 , Lauren M. Girard 3 , Donghui Li 3 , Ping Chang 3 , Kanwal Raghav 3 , Jeff Morris 4 , Robert A. Wolff 3 , Asif Rashid 5 , Hesham M. Amin 6 and Ahmed Kaseb 3 1 Department of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 2 Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 3 Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 4 Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 5 Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 6 Department of Hemopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 7 Department of Clinical Oncology, Assiut University Hospitals, Faculty of Medicine, Assiut, Egypt Correspondence to: Ahmed Kaseb, email: aokaseb@mdanderson.org Manal M. Hassan, email: mhassan@mdanderson.org Keywords: angiogenesis; angiopoietin-1; angiopoietin-2; cirrhosis; hepatocellular carcinoma Abbreviations: Ang-1: angiopoietin-1; Ang-2: angiopoietin-2; HCC: hepatocellular carcinoma; mAB: monoclonal antibody; OS: overall survival Received: August 08, 2018 Accepted: November 16, 2018 Published: December 28, 2018 ABSTRACT Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) play critical roles in angiogenesis in hepatocellular carcinoma (HCC). In addition, recent data suggest that Ang-1/Ang-2 are involved in regulating the immune response. The aim of our study was to explore the clinical prognostic significance of plasma Ang-1 and Ang-2 in HCC. We prospectively enrolled and collected data and blood samples from 767 HCC patients treated at MD Anderson Cancer Center between 2001 and 2014. Controls consisted of cirrhotic patients ( n = 75) and healthy volunteers ( n = 200). The cutoff value was the median level of each angiogenic factor. Overall survival (OS) was estimated by Kaplan–Meier curves and compared by the log-rank test. Higher plasma Ang-2 was significantly associated with advanced clinicopathologic features of advanced HCC and lower OS. Median OS was 61.8 months (95% confidence interval [CI], 45.1–78.5 months) for low Ang-2 compared with 28.5 months (95% CI, 24.8–32.1 months) for high Ang-2 ( p < 0.001). In contrast, higher Ang-1 was associated with longer OS. Median OS was 37.2 months (95% CI, 31.0–43.4 months) for high Ang-1 compared with 26.2 months (95% CI, 22.2–30.3 months) for those with low Ang-1 (p = 0.043). In conclusion, our findings indicate that plasma Ang-1 and Ang-2 levels are potential diagnostic and prognostic biomarkers in HCC.